Project Title: Tumor-targeted nanoparticle-based delivery system for imaging and treatment of cancer Project Summary Early detection of cancer substantially increases the probability of its successful and effective treatment. Theranostics is an emerging field in medical research that can potentially improve overall patient therapy and outcome by combining diagnostic and specific therapeutic properties. Although nanoparticles allow for distinct advantages in the field of therapy of different diseases, a combination of both diagnostic and therapeutic modalities in a single nanoparticle may be associated with certain difficulties. Therefore, it may be ideal to develop a separated, but integrated multi-particle system for theranostics. The efficacy of the cancer detection by magnetic resonance imaging (MRI) and chemotherapy of primary tumors and metastases can be significantly improved by targeting of nanoparticles containing a contrast agent or anticancer drug specifically to cancer cells. Consequently, the overall goal of the planned investigations consists of the development, characterization, and preclinical in vivo testing of multi-particle cancer-targeted system for diagnostics by MRI and chemotherapy of primary tumors and metastases. In the present theranostic study, manganese oxide nanoparticles (Mn3O4) will be used as MRI contrast agents; poor water-soluble anticancer drug paclitaxel (PTX) ? as an anticancer drug; neutral liposomes ? as carriers for PTX; a modified luteinizing hormone releasing hormone (LHRH) peptide ? as targeting moiety. The developed multi-particle theranostic system will be tested in vitro and in vivo using murine models of human ovarian and lung cancers. However, the proposed approach may be extended for other types of carriers/particles, contrast agents, and anticancer drugs as well as other types of cancer. The specific aims of the proposal are: (1) To synthesize and characterize cancer- targeted nanoparticles for imaging and treatment of cancers; (2) To evaluate the efficacy of the synthesized nanoparticles as MRI contrast agents for the detection of primary tumors and metastases in vivo using murine models of lung and ovarian cancers; (3) To evaluate the effect of formulation and drug delivery route on whole body tissue disposition and pharmacokinetics of paclitaxel and (4) To examine in vivo antitumor efficacy and adverse side effects of combined imaging and chemotherapy with PEGylated cancer-targeted liposomes containing PTX using orthotopic murine model of lung cancer after intravenous and inhalation delivery. It is expected that proposed approach and the use of the developed cancer-targeted nanoparticle-based MRI contrast agents and chemotherapeutic drug will substantially enhance the efficacy of the detection of primary tumors and metastases and therapy for cancers, while limiting adverse side effects of the treatments. The planned studies have the potential to significantly impact the field of imaging and drug delivery and to improve the efficiency of therapy of lung and other types of cancer.